Angiogenesis is considered as an important process in tumor growth, metastasis of hepatocellular carcinoma (HCC) and associated with cancer progression, suggesting that an important research and development field of clinical molecular targeted drugs for HCC. However, the molecular mechanisms underlying tumor angiogenesis in HCC remains elusive. In the current study, we demonstrate that upregulation of AMYB proto-oncogene-like 1 (MYBL1) was associated with high endothelial vessel (EV) density and contributed to poor prognosis of HCC patient. Functionally, MYBL1 overexpressing enhanced the capacity of HCC cells to induce tube formation, migration of HUVECs, neovascularization in CAMs, finally, enhanced HCC cells metastasis, while silencing MYBL1 had the converse effect. Furthermore, HCC cells with high MYBL1 expression were more resistance to sorafenib treatment. We observed that CD31 staining was significantly increased in tumors formed by MYBL1-overexpressing cells but decreased in MYBL1-silenced tumors. Mechanistically, MYBL1 binds to the ANGPT2 promoter and transcriptionally upregulate ANGPT2 mRNA expression. Strikingly, treatment with monoclonal antibody against ANGPT2 significantly inhibited the growth of MYBL1-overexpressing tumors and efficiently impaired angiogenesis. Furthermore, the histone post-translational factors: protein arginine methyltransferase 5 (PRMT5), MEP50, and WDR5 were required for MYBL1-mediated ANGPT2 upregulation. Importantly, we confirmed the correlation between MYBL1 and ANGPT2 expression in a large cohort of clinical HCC samples and several published datasets in pancreatic cancer, esophageal carcinoma, stomach adenocarcinoma, and colon cancer. Our results demonstrate that MYBL1 upregulated the ANGPT2 expression, then induced angiogenesis and confer sorafenib resistance to HCC cells, and MYBL1 may represent a novel prognostic biomarker and therapeutic target for patients with HCC.
The juxtaglomerular cell tumor (JCT) is a rare renal tumor. We re‐evaluated the clinicopathologic features of 21 JCTs to summarize their variable morphologies. Immunohistochemical, fluorescent in situ hybridization and periodic acid–Schiff stains were routinely performed, and four JCT cases were detected via transmission electron microscopy. The 21 JCTs involved five males and 16 females, ranging in age from 19 years to 69 years (mean, 36.9 years; median, 34 years). The tumors were composed of large, small, or spindle cells with a round, oval or polygonal shape, arranged in various growth patterns. Both necrosis (1/21) and mitosis (2/21, with 1/50HFP, 8/50HFP) was rarely appreciated. All cases were immunoreactive for renin and CD34 (21/21), and few were positive for α‐SMA (13/21;11/21, focally; 2/21, diffusely,), CD117 (9/21, focally) and synaptophysin (3/21, focally). Ultrastructurally, all four cases exhibited secretory granules in varying sizes in the cytoplasm, two of which exhibited cellular junctions. Almost all cases (20/21) had a favorable prognosis, but one succumbed due to bone and hepatic metastases, which corresponds to malignant JCT. Our study demonstrates that JCTs may have atypical clinical presentations and variable histologic appearances. A familiarity with these features may contribute to a correct diagnosis.
Accumulating evidence demonstrates that dysregulation of ubiquitin-mediated degradation of oncogene or suppressors plays an important role in several diseases. However, the function and molecular mechanisms of ubiquitin ligases underlying hepatocellular carcinoma (HCC) remain elusive. In the current study, we show that overexpression of TRIM54 was associated with HCC progression. TRIM54 overexpression facilitates proliferation and lung metastasis; however, inhibition of TRIM54 significantly suppressed HCC progression both in vitro and in vivo. Mechanically, we demonstrated that TRIM54 directly interacts with Axis inhibition proteins 1 (Axin1) and induces E3 ligase-dependent proteasomal turnover of Axin1 and substantially induces sustained activation of wnt/β-catenin in HCC cell lines. Furthermore, we showed that inhibition of the wnt/β-catenin signaling pathway via small molecule inhibitors significantly suppressed TRIM54-induced proliferation. Our data suggest that TRIM54 might function as an oncogenic gene and targeting the TRIM54/Axin1/β-catenin axis signaling may be a promising prognostic factor and a valuable therapeutic target for HCC.
Background: At present, the surgical treatment of sinusitis with nasal polyps has made great progress, but its recurrence rate is still high. Therefore, this time, meta-analysis is used to study the therapeutic effect of endoscopic sinus surgery on children with chronic sinusitis with nasal polyps, analyze its effectiveness and safety, and provide theoretical basis for clinical treatment.Methods: Boolean logic searching was adopted to retrieve articles from various databases, including PubMed, Medline, and Chinese National Knowledge Infrastructure (CNKI), published from the establishment of the database to December 30, 2021. The following search terms were used: "endoscopic sinus surgery", "antrochoanal polyps", "chronic sinusitis with nasal polyps", and "nasal polyps". Comparative studies on traditional surgical treatment and endoscopic sinus surgery were also screened out. Review Manager was utilized for meta-analysis.Results: A total of 9 references were included in the study, and most of them were low risk bias (medium and high quality). Meta-analysis showed that there was no statistical heterogeneity between the control group and the experimental group (Chi 2 =0.03, I 2 =0%, P=0.98). According to the fixed effect model analysis, the number of patients with polyp formation in the experimental group was significantly less than that in the control group (Z=2.65, P=0.008). Compared with the control group, there is no statistical heterogeneity in the postoperative recurrence (Chi 2 =1.59, I 2 =0%, P=0.45). According to the analysis of fixed effect model, the postoperative recurrence in the experimental group is significantly less than that in the control group (Z=2.92, OR =2.78, 95% CI: 1.40-5.52, P=0.004). Compared with the control group, the results of postoperative visual analogue scale (VAS) were statistically different (Chi 2 =12.63, I 2 =84%, P=0.002). According to the random effect model analysis, the VAS score of the experimental group was significantly lower than that of the control group (Z=18.06, MD =4.51, 95% CI: 3.96-5.05, P<0.00001).Discussion: Endoscopic sinus surgery could reduce the postoperative recurrence and pain of patients, and showed high curative effects and safety in the treatment of children with chronic sinusitis with nasal polyps.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.